Production method of carbonyl compound

ABSTRACT

The present invention is to provide a method of producing a carbonyl compound at a higher yield. The method of producing a carbonyl compound according to the present invention produces a carbonyl compound represented by general formula (I) by subjecting a compound represented by general formula (II) to dealkoxycarbonylation in the presence of an organic carboxylic acid salt of a tertiary amine. 
     
       
         
         
             
             
         
       
     
     In the formula, R represents an alkyl group having from 1 to 4 carbons.

TECHNICAL FIELD

The present invention relates to a method of producing a carbonylcompound, and particularly relates to a method of producing a carbonylcompound by subjecting a β-ketoester compound to dealkoxycarbonylation.

BACKGROUND ART

Patent Document 1 describes a certain type of 2-(halogenated hydrocarbonsubstituted)-5-benzyl-1-azolylmethylcyclopentanol derivative as acompound that can be used as an active ingredient for agricultural andhorticultural chemicals, industrial material protectants, and the like.Patent Document 1 also describes a method of producing a2-benzyl-5,5-bis(hydroxymethyl)-cyclopentanone derivative having aprotected hydroxy group from a 1-benzyl-2-oxocyclopentane carboxylicacid alkyl ester derivative, which is a 11-ketoester compound, as a partof a step in the production method of this derivative.

CITATION LIST Patent Literature

[Patent Document 1] WO/2011/070771 (published on Jun. 16, 2011)

SUMMARY OF INVENTION Technical Problem

In order to produce a 2-(halogenated hydrocarbonsubstituted)-5-benzyl-1-azolylmethylcyclopentanol derivative, which isused as an active ingredient of agricultural or horticultural chemicalsand the like, at lower cost and in a large quantity, the yield of a2-benzyl-5,5-bis(hydroxymethyl)-cyclopentanone derivative having aprotected hydroxy group needs to be enhanced.

The present invention is completed in light of the problems describedabove. An object of the present invention is to provide a novelproduction method that can produce a carbonyl compound from β-ketoestercompound at a higher yield.

Solution to Problem

To solve the above problems, the method of producing a carbonyl compoundaccording to the present invention is a method of producing a carbonylcompound represented by general formula (I) below from a compoundrepresented by general formula (II) below, the method comprising a stepof subjecting the compound represented by general formula (II) below todealkoxycarbonylation in the presence of an organic carboxylic acid saltof a tertiary amine.

In general formula (II), Z¹ represents a substituted or unsubstitutedalkyl group, cycloalkyl group, aryl group, or heterocyclic group; Z³ andZ² each independently represent a hydrogen atom, a substituted orunsubstituted alkyl group, cycloalkyl group, aryl group, or heterocyclicgroup; and R represents an alkyl group having from 1 to 4 carbons. Z¹and Z² may be bonded to each other.

In general formula (I), Z¹, Z², and Z³ are the same as Z¹, Z², and Z³ ingeneral formula (II) above, respectively.

Advantageous Effects of Invention

By the method of producing a carbonyl compound according to the presentinvention, a carbonyl compound can be produced at a high yield from a11-ketoester compound.

DESCRIPTION OF EMBODIMENTS

As a result of diligent research, the present inventors have found thatthe yield of a 5-benzyl-2,2-bis(hydroxymethyl) cyclopentanone derivativehaving a protected hydroxy group can be enhanced by performing areaction using an organic carboxylic acid salt of a tertiary amine in aproduction step for obtaining a 5-benzyl-2,2-bis(hydroxymethyl)cyclopentanone derivative having a protected hydroxy group from a1-benzyl-3,3-bis(hydroxymethyl)-2-oxocyclopentane carboxylic acid alkylester derivative having a protected hydroxy group. In addition, thepresent inventors have found that a carbonyl compound can also beproduced at a high yield by using an organic carboxylic acid salt of atertiary amine in a reaction using another β-ketoester compound. As aresult, the present invention has been completed.

An embodiment of the method of producing a carbonyl compound accordingto the present invention will be described hereinafter.

The method of producing a carbonyl compound according to the presentinvention is a method of producing a carbonyl compound represented bygeneral formula (I) below from a β-ketoester compound (hereinafter,referred to as a “compound (II)”) represented by general formula (II)below, wherein the method produces a carbonyl compound represented bygeneral formula (I) by subjecting the compound (II) todealkoxycarbonylation in the presence of an organic carboxylic acid saltof a tertiary amine.

In the formula, Z¹ represents an alkyl group, cycloalkyl group, arylgroup, or heterocyclic group, and the alkyl group, cycloalkyl group,aryl group, and heterocyclic group may have a substituent.

The number of carbons in the alkyl group of Z¹ is not particularlylimited; however, the alkyl group can be exemplified by an alkyl grouphaving from 1 to 8 carbons. Examples of the alkyl group having from 1 to8 carbons include an ethyl group, methyl group, (1-methyl)ethyl group,n-propyl group, 1-methylpropyl group, 2-methylpropyl group,1,1-dimethylethyl group, n-butyl group, n-pentyl group, n-hexyl group,n-heptyl group, n-octyl group, and the like.

The number of carbons constituting the ring of the cycloalkyl group ofZ¹ is not particularly limited; however, the cycloalkyl group can beexemplified by a cycloalkyl group having from 3 to 6 carbons. Examplesof the cycloalkyl group having from 3 to 6 carbons include a cyclopropylgroup, cyclobutyl group, cyclopentyl group, cyclohexyl group, and thelike.

Examples of the aryl group of Z¹ include a phenyl group, naphthyl group,indene group, azulene group, diphenyl group, and the like.

The number of atoms constituting the ring of a heterocyclic group of Z¹is not particularly limited; however, the heterocyclic group can beexemplified by an aliphatic heterocyclic group having from 3 to 6members and an aromatic heterocyclic group having from 5 or 6 members.Examples of a heterocyclic ring constituting the aliphatic heterocyclicring having from 3 to 6 members include azetidine, aziridine,piperidine, piperazine, morpholine, pyrrolidine, oxetane,tetrahydrofuran, tetrahydropyran, and the like. Furthermore, examples ofa heterocyclic ring constituting the aromatic heterocyclic group havingfrom 5 to 6 members include thiophene, pyridine, thiazole, furan,pyrrole, oxazole, isoxazole, isothiazole, triazole, furazan, imidazole,pyrazole, pyrazine, pyrimidine, triazine, pyridazine, and the like.Examples thereof also include condensed heterocyclic rings, such asindole, benzofuran, benzothiophene, quinoline, quinoxaline; and thelike.

Examples of the substituent that can be contained in the alkyl group,cycloalkyl group, aryl group, and heterocyclic group of Z¹ may have ahalogen atom, an aliphatic hydrocarbon group, an aromatic hydrocarbongroup, an aromatic heterocyclic group, an aliphatic hydrocarbon group inwhich at least one hydrogen atom is substituted with an aromatichydrocarbon group or aromatic heterocyclic group, an alkoxy group, acarbonyloxyalkyl group, an amide group, a cyano group, a nitro group,and the like. Furthermore, a hydrogen atom in these substituents may besubstituted with a halogen atom, hydroxy group, alkoxy group, alkylgroup, haloalkyl group, aromatic hydrocarbon group, aromaticheterocyclic group, and the like. Furthermore, the hydroxy group may beprotected by a protecting group that protects the hydroxy group.

Z² and Z³ each independently represent a hydrogen atom, alkyl group,cycloalkyl group, aryl group, or heterocyclic group, and the alkylgroup, cycloalkyl group, aryl group, and heterocyclic group may have asubstituent. Examples of the alkyl group, cycloalkyl group, aryl group,heterocyclic group, and the substituent that can be contained in thesealkyl group, cycloalkyl group, aryl group, and heterocyclic group of Z²and Z³ are the same as the alkyl group, cycloalkyl group, aryl group,heterocyclic group, and the substituent that can be contained in thesealkyl group, cycloalkyl group, aryl group, and heterocyclic group of Z¹respectively.

Z² and Z³ may be the same or different from each other.

Z¹ and Z² may be bonded to each other and, together with a carbon atomto which Z¹ is bonded and a carbon atom to which Z² is bonded, form aring.

R represents an alkyl group having from 1 to 4 carbons. Examples thereofinclude a methyl group, ethyl group, (1-methyl)ethyl group, n-propylgroup, 1-methylpropyl group, 2-methylpropyl group, n-butyl group,1,1-dimethylethyl group, and the like.

Examples of the tertiary amine constituting the organic carboxylic acidsalt of a tertiary amine include aliphatic amines such astrimethylamine, triethylamine, ethyldimethylamine, tri-n-propylamine,triisopropylamine, tri-n-butylamine, triisobutylamine,tri-sec-butylamine, tri-tert-butylamine, tri-n-pentylamine,tri-n-hexylamine, tri-n-octylamine, diethylisopropylamine,diisopropylethylamine, tri cyclopropylamine, tricyclobutylamine,tetramethylethylene diamine, tricyclopentylamine, andtricyclohexylamine; nitrogen-containing heterocyclic aliphatic aminessuch as N-methylpyrrolidine, N-ethylpyrrolidine, N-methylpiperidine,N-ethylpiperidine, N-n-butylpiperidine, N-methylhexamethylene imine,N-ethylhexamethylene imine, N-methylmorpholine, N-ethylmorpholine,N-butylmorpholine, N,N′-dimethylpiperazine, N,N′-diethylpiperazine,1,5-diazabicyclo[4.3.1]non-5-ene, 1,4-diazabicyclo[2.2.2]octane, and1,8-diazabicyclo[5.4.0]undec-7-ene; and nitrogen-containing heterocyclicaromatic amines such as pyridine, picoline, and lutidine. Among these,triethylamine, trimethylamine, ethyldimethylamine, N-methylpyrrolidine,pyridine, collidine, or picoline is preferred, triethylamine,trimethylamine, pyridine, or picoline is more preferred, triethylamineor pyridine is even more preferred, and triethylamine is particularlypreferred.

As the organic carboxylic acid constituting the organic carboxylic acidsalt of a tertiary amine, organic monocarboxylic acids are preferred,saturated or unsaturated aliphatic monocarboxylic acids are morepreferred, and saturated aliphatic monocarboxylic acids are even morepreferred. The numbers of carbons of the saturated aliphatic carboxylicacid is preferably from 1 to 8, and more preferably from 1 to 4.Examples of the organic carboxylic acid include formic acid, aceticacid, propionic acid, butyric acid, isobutyric acid, valeric acid, andisovaleric acid. Among these, formic acid, acetic acid, and propionicacid are preferred, and acetic acid is particularly preferred.

From the above facts, preferable specific examples of the organiccarboxylic acid salt of a tertiary amine include acetate oftrimethylamine, formic acid salt of triethylamine, acetate oftrimethylamine, propionic acid salt of triethylamine, acetate ofpyridine, acetate of 2-picoline, acetate of 3-picoline, acetate of4-picoline, and the like. Among these, acetate of triethylamine oracetate of pyridine is preferred.

The amount of the organic carboxylic acid salt of a tertiary amine is,in terms of moles, for example, from 0.3 to 10 times, preferably from0.5 to 5 times, and more preferably from 0.8 to 3 times, relative to theamount of the compound (II).

The organic carboxylic acid salt of a tertiary amine may be produced byadding the tertiary amine and the organic carboxylic acid to a reactionsystem. Addition of the tertiary amine and the organic carboxylic acidis not limited to separate addition of the tertiary amine and theorganic carboxylic acid, and may be carried out by adding a premixedmixture of the tertiary amine and the organic carboxylic acid to areaction system. The mixing ratio of the tertiary amine to the organiccarboxylic acid may be 1:1. However, when a reaction is carried out fora compound in which the yield is expected to drop in a reaction underacidic conditions, as in the compound (IIc) and the compound (IId) to bedescribed later, and the like, it is preferable to use a larger amountof tertiary amine than organic carboxylic acid in order to preventexcessive organic carboxylic acid, which results in an acidic reactionsystem. In this case, the amount of tertiary amine is, in terms ofmoles, for example, from 1.01 to 5 times, and preferably from 1.05 to 2times, relative to the amount of organic carboxylic acid.

Additionally, an alkali metal salt of an organic carboxylic acid may befurther added to the reaction system. When reaction progress is slow,the reaction can be accelerated by adding an alkali metal salt of anorganic carboxylic acid, and the yield can be improved thereby. Thealkali metal salt of an organic carboxylic acid may be added to thereaction system in advance, or may be added to the reaction systemduring the reaction.

Examples of the organic carboxylic acid constituting the alkali metalsalt of an organic carboxylic acid are the same as the organiccarboxylic acids constituting the organic carboxylic acid salt of atertiary amine described above. Furthermore, the organic carboxylic acidconstituting the alkali metal salt of an organic carboxylic acid may bethe same as or different from the organic carboxylic acid constitutingthe organic carboxylic acid salt of a tertiary amine used in thereaction. However, it is preferable to use an organic carboxylic acidthat is the same as that used in the reaction. Additionally, examples ofthe alkali metal constituting the alkali metal salt of an organiccarboxylic acid include sodium and potassium. For example, when acetateof triethylamine is used as the organic carboxylic acid salt of atertiary amine, sodium acetate and potassium acetate are preferred asthe alkali metal salt of an organic carboxylic acid.

The dealkoxycarbonylation reaction may also be performed in a solvent.The solvent is not particularly limited as long as the solvent does notparticipate in the reaction. For example, amides such asN,N-dimethylformamide, N,N-dimethylacetamide, and N-methyl-2-pyrrolidonecan be advantageously used. Furthermore, the solvent may be a mixedsolvent with another solvent that can be mixed with these solvents (forexample, toluene, DMSO, and the like).

The reaction temperature is, for example, from 0 to 250° C., preferablyfrom room temperature to 200° C., and more preferably from 50 to 180° C.Furthermore, the reaction time is, for example, from 0.05 hours to a fewdays, preferably from 0.1 hours to 5 days, and more preferably from 0.5hours to 2 days.

Note that, even when the reaction is not performed under inert gas, thereaction proceeds without problems. However, depending on the type ofamine that is used, when the reaction takes place for a long time at ahigh temperature and when the reaction proceeds in the air, problems,such as coloration of the reaction liquid caused by being affected byair oxidation, may occur. In such a case, it is more preferable toperform the reaction under an inert gas (for example, nitrogen, argon,and the like) atmosphere.

Other reaction conditions can be easily designed and set by a personskilled in the art by referring to conventionally known productionmethods.

In the present specification, “dealkoxycarbonylation” indicates that—CO₂R is eventually substituted with a hydrogen atom. From theperspective of obtaining a carbonyl compound by removing —CO₂R from aβ-ketoester compound, dealkoxycarbonylation is same as hydrolysis anddecarboxylation of the β-ketoester compound. However, since, in theproduction method using organic carboxylic acid salt of a tertiary amineof the present invention, the reaction proceeds in the absence of water,the “dealkoxycarbonylation” in the present invention is clearlydistinguished from a reaction including hydrolysis that requires water.Note that, when water is present in the reaction system, a hydroxide ionmay be generated from the water molecule under a condition containingbases, thereby causing undesired side reactions. Therefore, it ispreferred that the system contains no water.

In the production method according to the present invention, since thereaction is performed using a salt of a tertiary amine, but not an acidor alkali, it is possible to perform the reaction under a neutral oralmost neutral condition. Therefore, even for a compound which isunstable to an acid or alkali and the yield of which is anticipated tobe lowered under acidic conditions or basic conditions, the reaction canbe performed with a high yield.

The reaction mechanism of the dealkoxycarbonylation in the method ofproducing a carbonyl compound according to the present invention ispresumed to include the following reaction mechanism, for example.

First, an acid anhydride is produced by replacing the alkoxy group inthe compound (II) with an organic carboxylate anion. Because thecarboxylic acid salt of a tertiary amine is a proton source, the alkoxygroup produced by replacement becomes alkyl alcohol, and aβ-ketocarboxylic acid is produced by a reaction between the alkylalcohol and the acid anhydride. A compound represented by generalformula (I) is formed by decarboxylation of the producedβ-ketocarboxylic acid. Meanwhile, since the organic carboxylic acidalkyl ester produced by the substitution has a relatively low boilingpoint, it is removed to outside the system.

However, in the method of producing a carbonyl compound according to thepresent invention, the reaction mechanism is not limited to the abovereaction mechanism or other specific reaction mechanisms as long as thereaction proceeds using an organic carboxylic acid salt of a tertiaryamine. Furthermore, the method is not limited to cases where thereaction proceeds by a single reaction mechanism, and the method may bea method in which the reaction proceeds by a plurality of reactionmechanisms.

A preferable aspect of the method of producing a carbonyl compoundaccording to the present invention is a method of producing a carbonylcompound represented by general formula (Ia). The method produces acarbonyl compound represented by general formula (Ia) by subjecting aβ-ketoester compound having a cyclopentane ring represented by generalformula (IIa) below (hereinafter, referred to as a “compound (IIa)”) todealkoxycarbonylation in the presence of an organic carboxylic acid saltof a tertiary amine.

In the formula, Y represents an alkyl group or haloalkyl group havingfrom 1 to 6 carbons, an alkenyl group or haloalkenyl group having from 2to 6 carbons, an alkynyl group or haloalkynyl group having from 2 to 6carbons, or a group in which a part of hydrogen atoms of the alkylgroup, haloalkyl group, alkenyl group, haloalkenyl group, alkynyl group,or haloalkynyl group is substituted with —OG (G represents a protectinggroup of a hydroxy group).

Examples of the alkyl group having from 1 to 6 carbons include a methylgroup, ethyl group, (1-methyl)ethyl group, n-propyl group,1-methylpropyl group, 2-methylpropyl group, n-butyl group, 1-methylbutylgroup, 2-methylbutyl group, 1-ethylpropyl group, 1,1-dimethylethylgroup, and the like. Among these, an alkyl group having from 1 to 4carbons is preferable. A methyl group and an ethyl group are morepreferable, and a methyl group is even more preferable.

Examples of the haloalkyl group having from 1 to 6 carbons include achloromethyl group, dichloromethyl group, trichloromethyl group,2-chloroethyl group, 1-chloroethyl group, 2,2-dichloroethyl group,1,2-dichloroethyl group, 2,2,2-trichloroethyl group, 3-chloropropylgroup, 2,3-dichloropropyl group, 1-chloro-1-methylethyl group,2-chloro-1-methylethyl group, 2-chloropropyl group, 4-chlorobutyl group,5-chloropentyl group, fluoromethyl group, difluoromethyl group,trifluoromethyl group, 2-fluoroethyl group, 1-fluoroethyl group,2,2-difluoroethyl group, 1,2-difluoroethyl group, 2,2,2-trifluoroethylgroup, 3-fluoropropyl group, 2,3-difluoropropyl group,1-fluoro-1-methylethyl group, 2-fluoro-1-methylethyl group,2-fluoropropyl group, 3,3,3-trifluoropropyl group,2,2,3,3-tetrafluoropropyl group, 2,2,3,3,3-pentafluoropropyl group,4-fluorobutyl group, 5-fluoropentyl group, bromomethyl group,dibromomethyl group, tribromomethyl group, 2-bromoethyl group,1-bromoethyl group, 2,2-dibromoethyl group, 1,2-dibromoethyl group,2,2,2-tribromoethyl group, 3-bromopropyl group, 2,3-dibromopropyl group,1-bromo-1-methylethyl group, 2-bromo-1-methylethyl group, 2-bromopropylgroup, 4-bromobutyl group, 5-bromopentyl group, iodomethyl group,diiodomethyl group, 2-iodoethyl group, 1-iodoethyl group,2,2-diiodoethyl group, 1,2-diiodoethyl group, 2,2,2-triiodoethyl group,3-iodopropyl group, 2,3-diiodopropyl group, 1-iodo-1-methylethyl group,2-iodo-1-methylethyl group, 2-iodopropyl group, 4-iodobutyl group, andthe like. Among these, a haloalkyl group having from 1 to 4 carbons ispreferable, and a haloalkyl group having from 1 to 3 carbons is morepreferable.

Examples of the alkenyl group having from 2 to 6 carbons include anethenyl group, 1,2-dimethylethenyl group, 4-methyl-1,3-butadienyl group,1-propenyl group, 2-propenyl group, 2-methyl-2-propenyl group,3-methyl-2-propenyl group, 2-butenyl group, 3-butenyl group,3-methyl-3-butenyl group, and the like. Among these, an alkenyl grouphaving from 2 to 4 carbons is preferable.

Examples of the haloalkenyl group having from 2 to 6 carbons include a2-chloroethenyl group, 2,2-dichloroethenyl group, 2-chloro-2-propenylgroup, 3,3-dichloro-2-propenyl group, 2,3-dichloro-2-propenyl group,3,3-dichloro-2-methyl-2-propenyl group, 3-chloro-2-butenyl group,2-fluoroethenyl group, 2,2-difluoroethenyl group, 2-fluoro-2-propenylgroup, 3,3-difluoro-2-propenyl group, 2,3-difluoro-2-propenyl group,3,3-difluoro-2-methyl-2-propenyl group, 3-fluoro-2-butenyl group,2-bromoethenyl group, 2,2-dibromoethenyl group, 2-bromo-2-propenylgroup, 3,3-dibromo-2-propenyl group, 2,3-dibromo-2-propenyl group,3,3-dibromo-2-methyl-2-propenyl group, 3-bromo-2-butenyl group,2-iodoethenyl group, 2,2-diiodoethenyl group, 2-iodo-2-propenyl group,3,3-diiodo-2-propenyl group, 2,3-diiodo-2-propenyl group, and the like.Among these, a haloalkenyl group having from 2 to 4 carbons ispreferable.

Examples of the alkynyl group having from 2 to 6 carbons include anethynyl group, 1-propynyl group, 2-propynyl group, 1-butynyl group,2-butynyl group, and the like. Among these, an alkynyl group having from2 to 4 carbons are preferable.

Examples of the haloalkynyl group having from 2 to 6 carbons include a2-fluoroethynyl group, 2-chloroethynyl group, 3-fluoro-2-propynyl group,3-chloro-2-propynyl group, 3-bromo-2-propynyl group, and the like. Amongthese, a haloalkynyl group having from 2 to 4 carbons is preferable.

The protecting group G in —OG is a protecting group that protects ahydroxy group. The protecting group is not particularly limited as longas the protecting group dissociates under a proper condition to form ahydroxy group. Examples of the protecting group G include a protectinggroup that dissociates under acidic conditions, a protecting group thatsplits under reducing conditions such as a hydrogenation reaction, andthe like.

n represents an integer from 0 to 6, and n is preferably from 0 to 3,and more preferably from 0 to 2. When n is 2 or greater, a plurality ofY may be the same or different each other. Furthermore, when n is 2 orgreater, two Y may be bonded to one carbon atom. Furthermore, when n is2 or greater, a plurality of Y may be bonded to each other and, togetherwith carbon atom(s) to which the plurality of Y are bonded, form a ring;

X represents a halogen atom, an alkyl group having from 1 to 4 carbons,a haloalkyl group having from 1 to 4 carbons, an alkoxy group havingfrom 1 to 4 carbons, a haloalkoxy group having from 1 to 4 carbons, aphenyl group, a cyano group, or a nitro group.

Examples of the halogen atom of X include a fluorine atom, chlorineatom, bromine atom, iodine atom, and the like. Among these, a fluorineatom, chlorine atom, and bromine atom are preferable, and a fluorineatom and chlorine atom are more preferable.

Specific examples of the alkyl group having from 1 to 4 carbons of Xinclude a methyl group, ethyl group, n-propyl group, isopropyl group,n-butyl group, isobutyl group, sec-butyl group, and tert-butyl group.Among these, an alkyl group having from 1 to 3 carbons is preferable. Analkyl group having from 1 to 2 carbons are more preferable, and a methylgroup is even more preferable.

Examples of the haloalkyl group having from 1 to 4 carbons of X includea dichloromethyl group, trichloromethyl group, 2-chloroethyl group,1-chloroethyl group, 2,2-dichloroethyl group, 1,2-dichloroethyl group,2,2,2-trichloroethyl group, 3-chloropropyl group, 2,3-dichloropropylgroup, 1-chloro-1-methylethyl group, 2-chloro-1-methylethyl group,2-chloropropyl group, 4-chlorobutyl group, fluoromethyl group,difluoromethyl group, trifluoromethyl group, 2-fluoroethyl group,1-fluoroethyl group, 2,2-difluoroethyl group, 1,2-difluoroethyl group,2,2,2-trifluoroethyl group, 3-fluoropropyl group, 2,3-difluoropropylgroup, 1-fluoro-1-methylethyl group, 2-fluoro-1-methylethyl group,2-fluoropropyl group, 3,3,3-trifluoropropyl group,2,2,3,3-tetrafluoropropyl group, 2,2,3,3,3-pentafluoropropyl group,4-fluorobutyl group, dibromomethyl group, tribromomethyl group,2-bromoethyl group, 2,2-dibromoethyl group, 1,2-dibromoethyl group,2,2,2-tribromoethyl group, 3-bromopropyl group, 2,3-dibromopropyl group,1-bromo-1-methylethyl group, 2-bromo-1-methylethyl group, 2-bromopropylgroup, diiodomethyl group, 2,2-diiodoethyl group, 1,2-diiodoethyl group,2,2,2-triiodoethyl group, 2,3-diiodopropyl group, 1-iodo-1-methylethylgroup, 2-iodo-1-methylethyl group, and the like. Among these, ahaloalkyl group having from 1 to 3 carbons are preferable, and ahaloalkyl group having 1 or 2 carbons is more preferable. A trihaloalkylgroup having 1 carbon is even more preferable.

Examples of the alkoxy group having from 1 to 4 carbons in X include amethoxy group, ethoxy group, n-propoxy group, and the like. Among these,an alkoxy group having from 1 to 3 carbons is preferable, and an alkoxygroup having 1 or 2 carbons is more preferable. A methoxy group is evenmore preferable.

Examples of the haloalkoxy group having from 1 to 4 carbons of X includea trifluoromethoxy group, difluoromethoxy group,1,1,2,2,2-pentafluoroethoxy group, 2,2-tifluoroethoxy group,2-tifluoroethoxy group, and the like. Among these, a haloalkoxy grouphaving from 1 to 3 carbons is preferable, and a haloalkoxy group having1 or 2 carbons is more preferable. A dihalomethoxy group andtrihalomethoxy group having 1 carbon are even more preferable.

m represents an integer from 0 to 5. m is preferably an integer from 0to 3, more preferably an integer from 0 to 2, and even more preferably 0or 1. When m is 2 or greater, a plurality of X may be the same ordifferent each other. When m is 1 or more, X may be positioned at anyone of 2 to 6 positions of the benzene ring; however, when m is 1, X ispreferably at a position that forms a 4-substituted benzyl.

R is the same as R in general formula (II) above.

The type and used amount of the organic carboxylic acid salt of atertiary amine, the type of solvent, the reaction conditions of thereaction, and the like used in the reaction that dealkoxycarbonylatesthe compound (IIa) are the same as the above-described type and usedamount of the organic carboxylic acid salt of a tertiary amine, type ofsolvent, reaction conditions, and the like.

Preferable examples of the compound (IIa) include a compound representedby general formula (IIa-1) below and a compound represented by generalformula (IIa-2) below.

A more preferable aspect of the method of producing a carbonyl compoundaccording to the present invention is a method of producing a carbonylcompound represented by general formula (Ib). The method produces acarbonyl compound represented by general formula (Ib) by subjecting aβ-ketoester compound having a cyclopentane ring represented by generalformula (IIb) below (hereinafter, referred to as “compound (IIb)”) todealkoxycarbonylation in the presence of an organic carboxylic acid saltof a tertiary amine.

In the formula, Y¹ and Y² each independently represent an alkyl group orhaloalkyl group having from 1 to 6 carbons, or a group in which a partof hydrogen atoms of the alkyl group or haloalkyl group are substitutedwith —OG¹ (G¹ represents a protecting group of a hydroxy group).

Examples of the alkyl group and haloalkyl group having from 1 to 6carbons of Y¹ and Y² are the same as those for the alkyl group andhaloalkyl group having from 1 to 6 carbons of Y described above.

The protecting group G¹ is a protecting group that protects a hydroxygroup. The protecting group is not particularly limited as long as theprotecting group dissociates under a proper condition to form a hydroxygroup. Examples of the protecting group G′ include a protecting groupthat dissociates under acidic conditions. Examples of the protectinggroup that dissociates under acidic conditions include an alkoxymethylgroup and alkoxyethyl group in which alkoxy moiety has from 1 to 4carbons (for example, methoxymethyl group, ethoxymethyl group, and thelike), an alkyl group having from 1 to 4 carbons (for example, methylgroup, ethyl group, t-butyl group, and the like), a substituted orunsubstituted benzyl group, a substituted or unsubstitutedtetrahydropyranyl group, a substituted or unsubstitutedtetrahydrofuranyl group, an allyl group, a silyl group (for example,triethylsilyl group, t-butyldimethylsilyl group, and the like), and thelike. Furthermore, the protecting group for two hydroxy groups may bebonded to each other; for example, and a case where two hydroxy groupsare protected at the same time by acetals, such as methylene acetal orethylidene acetal, is possible.

Furthermore, examples thereof also include a protecting group thatsplits under reducing conditions. Examples of the protecting group thatsplits under reducing conditions include a benzyl group, a substitutedor unsubstituted benzyl group, such as a p-methoxybenzyl group, and thelike.

Y¹ and Y² may be bonded to each other and, together with a carbon atomto which Y¹ and Y² are bonded, form a ring.

Furthermore, R, X, and m are the same as R, X, and m in general formula(II) above.

The type and used amount of the organic carboxylic acid salt of atertiary amine, the type of solvent, the reaction conditions of thereaction, and the like used in the reaction that dealkoxycarbonylatesthe compound (In) are the same as the above-described type and usedamount of the organic carboxylic acid salt of a tertiary amine, type ofsolvent, reaction conditions, and the like.

Another preferable aspect of the method of producing a carbonyl compoundaccording to the present invention is a method of producing a carbonylcompound represented by general formula (Ic) (hereinafter, referred toas “compound (Ic)”). The method produces a compound (Ic) by subjecting aβ-ketoester compound having a cyclopentane ring represented by generalformula (IIc) below (hereinafter, referred to as “compound (IIc)”) todealkoxycarbonylation in the presence of an organic carboxylic acid saltof a tertiary amine.

In the formula, G² and G³ each independently represent a protectivegroup that protects a hydroxy group, and, in particular, represents aprotective group that dissociates under acidic conditions. Note that G²and G³ may be bonded to each other and, together with oxygen atoms towhich, respectively, G² and G³ are bonded, carbon atoms to which,respectively, the oxygen atoms are bonded, and a carbon atom of thecyclopentane ring to which these carbon atoms are bonded, form a ring.

Examples of the protecting group in cases where G² and G³ are not bondedto each other include an alkoxymethyl group in which an alkoxy moietyhas from 1 to 4 carbons (for example, methoxymethyl group, ethoxymethylgroup, and the like), an alkoxyethyl group in which an alkoxy moiety hasfrom 1 to 4 carbons (for example, 1-ethoxyethyl group,1-methyl-1-methoxyethyl group, and the like), an alkyl group having from1 to 4 carbons (for example, t-butyl group, methyl group, and the like),a substituted or unsubstituted benzyl group, a substituted orunsubstituted tetrahydropyranyl group, a substituted or unsubstitutedtetrahydrofuranyl group, an allyl group, and a silyl group (for example,triethylsilyl group, t-butyldimethylsilyl group, and the like).

On the other hand, examples of the protecting group in cases where G²and G³ are bonded to each other include methylene acetal, ethylideneacetal, t-butylmethylidene ketal, 1-t-butylethylidene ketal,1-phenylethylidene ketal, acrolein acetal, isopropylidene ketal(acetonide), cyclopentylidene ketal, cyclohexylidene ketal,cycloheptylidene ketal, benzylidene acetal, p-methoxybenzylidene acetal,2,4-dimethoxybenzylidene ketal, 3,4-dimethoxybenzylidene ketal,2-nitrobenzylidene acetal, 4-nitrobenzylidene acetal, mesitylene acetal,1-naphthaldehyde acetal, benzophenone ketal, camphor ketal, menthoneketal, methoxymethylene acetal, ethoxymethylene acetal,dimethoxymethylene orthoester, 1-methoxyethylidene orthoester,1-ethoxyethylidene orthoester, methylidene orthoester, phthalideorthoester, 1,2-dimethoxyethylidene orthoester, α-methoxybenzylideneorthoester, 2-oxacyclopentylidene orthoester, butane-2,3-bis-acetal,cyclohexane-1,2-diacetal, bis-dihydropyran ketal, di-t-butylsilylene,1,3-(1,1,3,3-tetraisopropyl)disiloxanilidene, and1,1,3,3-tetra-t-butoxydisiloxanilidene.

Furthermore, R, X, and m are the same as R, X, and m in general formula(II) above.

The type and used amount of the organic carboxylic acid salt of atertiary amine, the type of solvent, the reaction conditions of thereaction, and the like used in the reaction that dealkoxycarbonylatesthe compound (IIc) are the same as the above-described type and usedamount of the organic carboxylic acid salt of a tertiary amine, type ofsolvent, reaction conditions, and the like.

G² and G³ are protecting groups that dissociate under acidic conditions.Therefore, when hydrolysis and decarboxylation reactions are used in anattempt to obtain the compound (Ic) from the compound (IIc), the yieldof the compound (Ic) decreases if the reaction is performed under acidicconditions. Meanwhile, when the inventors of the present applicationconducted various investigations, it was found that, when the compound(IIc) was hydrolyzed/decarboxylated under basic conditions, the yield ofthe compound (Ic) decreased due to the occurrence of side reactionsinvolving the opening of cyclopentane rings. Therefore, for a reactionto obtain the compound (Ic) from the compound (IIc), performing thereaction under a neutral or almost neutral condition is desired. Here,according to the production method of the present invention in whichdealkoxycarbonylation is performed using an organic carboxylic acid saltof a tertiary amine, it is possible to perform the reaction under aneutral or almost neutral condition. Therefore, the production method ofthe present invention in which dealkoxycarbonylation is performed usingan organic carboxylic acid salt of a tertiary amine exhibits excellenteffect especially in a method of producing the compound (Ic) from thecompound (IIc) for which performing the reaction under a neutral oralmost neutral condition is desired.

Furthermore, a side reaction in which a cyclopentane ring is opened uponperforming hydrolysis/decarboxylation under basic conditions can occurnot only in a reaction for the compound (IIc) but also in reactions forthe compound (IIa) and the compound (IIb) in which a cyclopentane ringis contained. Therefore, when it is not desirable to performhydrolysis/decarboxylation of the compound (IIa) and the compound (IIb)under acidic conditions due to some reason (for example, in cases wherethe yield will be decreased by performing hydrolysis/decarboxylationunder acidic conditions), the production method of the present inventionin which dealkoxycarbonylation is performed using an organic carboxylicacid salt of a tertiary amine is particularly preferably employed.

A preferable aspect in cases where G² and G³ are bonded to each other toform a ring is a method of producing a carbonyl compound represented bygeneral formula (Id). The method produces a carbonyl compoundrepresented by general formula (Id) by subjecting a β-ketoester compoundhaving a cyclopentane ring represented by general formula (IId) below todealkoxycarbonylation in the presence of an organic carboxylic acid saltof a tertiary amine.

In the formula, G⁴ and G⁵ each independently represent a hydrogen atom,an alkyl group having from 1 to 4 carbons, an alkenyl group having from1 to 4 carbons, a phenyl group, a naphthyl group, or a benzyl group. Aphenyl moiety of the phenyl group, naphthyl group, and benzyl group ofG⁴ and G⁵ may be substituted with an alkyl group having from 1 to 4carbons (for example, methyl group, ethyl group, and the like); analkoxy group having from 1 to 4 carbons (for example, methoxy group,ethoxy group, and the like); a nitro group; or a halogen atom (forexample, fluorine atom, chlorine atom, and the like). Note that G⁴ andG⁵ may be bonded to each other and, together with a carbon atom to whichG⁴ and G⁵ are bonded, form a ring. Among these, G⁴ and G⁵ are morepreferably each independently a hydrogen atom or an alkyl group havingfrom 1 to 4 carbons, such as a methyl group, ethyl group, and n-propylgroup; and even more preferably each independently a hydrogen atom,methyl group, or ethyl group. Furthermore, both of G⁴ and G⁵ areparticularly preferably a methyl group.

Furthermore, R, X, and m are the same as R, X, and m in general formula(II) above.

The type and used amount of the organic carboxylic acid salt of atertiary amine, the type of solvent, the reaction conditions of thereaction, and the like used in the reaction that dealkoxycarbonylatesthe compound (IId) are the same as the above-described type and usedamount of the organic carboxylic acid salt of a tertiary amine, type ofsolvent, reaction conditions, and the like.

A particularly preferable aspect of the method of producing a carbonylcompound according to the present invention is a method of producing acarbonyl compound represented by general formula (Ie). The methodproduces a carbonyl compound represented by general formula (Ie) bysubjecting a β-ketoester compound having a cyclopentane ring representedby general formula (IIe) below to dealkoxycarbonylation in the presenceof an organic carboxylic acid salt of a tertiary amine.

In the formula, G⁶ and G⁷ each independently represent a hydrogen atomor an alkyl group having from 1 to 4 carbons, such as a methyl group,ethyl group, and n-propyl group. Among these, G⁶ and G⁷ are preferablyeach independently a hydrogen atom, methyl group, or ethyl group.Furthermore, both of G⁶ and G⁷ are more preferably a methyl group.

X¹ represents a hydrogen atom, chlorine atom, or fluorine atom.

SUMMARY

The method of producing a carbonyl compound according to the presentinvention is a method of producing a carbonyl compound represented bygeneral formula (I) below from a compound represented by general formula(II) below, the method comprising a step of subjecting the compoundrepresented by general formula (II) below to dealkoxycarbonylation inthe presence of an organic carboxylic acid salt of a tertiary amine.

In general formula (II), Z¹ represents a substituted or unsubstitutedalkyl group, cycloalkyl group, aryl group, or heterocyclic group; Z³ andZ² each independently represent a hydrogen atom, a substituted orunsubstituted alkyl group, cycloalkyl group, aryl group, or heterocyclicgroup; and R represents an alkyl group having from 1 to 4 carbons. Z¹and Z² may be bonded to each other.

In general formula (I), Z¹, Z², and Z³ are the same as Z¹, Z², and Z³ ingeneral formula (II) above, respectively. Furthermore, in the method ofproducing a carbonyl compound according to the present invention, atertiary amine constituting the organic carboxylic acid salt of atertiary amine is preferably triethylamine, trimethylamine, pyridine, orpicoline.

Furthermore, in the method of producing a carbonyl compound according tothe present invention, an organic carboxylic acid constituting theorganic carboxylic acid salt of a tertiary amine is preferably analiphatic monocarboxylic acid.

Furthermore, in the method of producing a carbonyl compound according tothe present invention, an organic carboxylic acid salt of a tertiaryamine is preferably acetate of triethylamine or pyridine.

Furthermore, in the method of producing a carbonyl compound according tothe present invention, an alkali metal salt of an organic carboxylicacid is preferably further added to the reaction system.

Furthermore, in the method of producing a carbonyl compound according tothe present invention, the compound represented by general formula (II)above is preferably a compound represented by general formula (IIa)below; and the carbonyl compound represented by general formula (I)above is preferably a carbonyl compound represented by general formula(Ia) below.

In general formula (IIa), R represents an alkyl group having from 1 to 4carbons, Y represents an alkyl group or haloalkyl group having from 1 to6 carbons, an alkenyl group or haloalkenyl group having from 2 to 6carbons, an alkynyl group or haloalkynyl group having from 2 to 6carbons, or a group in which a part of hydrogen atoms of the alkylgroup, haloalkyl group, alkenyl group, haloalkenyl group, alkynyl group,or haloalkynyl group is substituted with —OG (G represents a protectinggroup of a hydroxy group); and n is an integer from 0 to 6. When n is 2or greater, a plurality of Y may be the same or different. When n is 2or greater, a plurality of Y may be bonded to each other and, togetherwith carbon atom(s) to which the plurality of Y are bonded, form a ring.X represents a halogen atom, an alkyl group having from 1 to 4 carbons,a haloalkyl group having from 1 to 4 carbons, an alkoxy group havingfrom 1 to 4 carbons, a haloalkoxy group having from 1 to 4 carbons, aphenyl group, a cyano group, or a nitro group; and m is an integer from0 to 5, when m is 2 or greater, a plurality of X may be the same ordifferent.

In general formula (Ia), X, Y, m, and n are the same as X, Y, m, and nin general formula (IIa) above, respectively.

Furthermore, in the method of producing a carbonyl compound according tothe present invention, the compound represented by general formula (IIa)above is preferably a compound represented by general formula (IIb)below; and the carbonyl compound represented by general formula (Ia)above is preferably a carbonyl compound represented by general formula(Ib) below:

In general formula (IIb), Y¹ and Y² each independently represent analkyl group or haloalkyl group having from 1 to 6 carbons, or a group inwhich a part of hydrogen atoms of the alkyl group or haloalkyl group issubstituted with —OG¹ (G¹ represents a protecting group of a hydroxygroup), and Y¹ and Y² may be bonded to each other and, together with acarbon atom to which Y¹ and Y² are bonded, form a ring. R, X, and m arethe same as R, X, and m in general formula (IIa) above, respectively.

In general formula (Ib), X, Y¹, Y², and m are the same as X, Y¹, Y², andm in general formula (In) above, respectively.

Furthermore, in the method of producing a carbonyl compound according tothe present invention, the compound represented by general formula (IIb)above is preferably a compound represented by general formula (IIc)below; and the carbonyl compound represented by general formula (Ib)above is preferably a carbonyl compound represented by general formula(Ic) below.

In general formula (IIc), G² and G³ each independently represent aprotecting group that dissociates under acidic conditions, and G² and G³may be bonded to each other. R, X, and m are the same as R, X, and m ingeneral formula (IIa) above, respectively.

In general formula (Ic), X, G², G³, and m are the same as X, G², G³, andm in general formula (IIc) above, respectively.

Furthermore, in the method of producing a carbonyl compound according tothe present invention, it is preferable if the organic carboxylic acidsalt of a tertiary amine is produced in the reaction system by addingthe tertiary amine to the compound represented by general formula (IIc)above and then adding an organic carboxylic acid in an amount smallerthan the added amount of the tertiary amine, and dealkoxycarbonylationis performed.

Furthermore, in the method of producing a carbonyl compound according tothe present invention, the compound represented by general formula (IIc)above is preferably a compound represented by general formula (IId)below; and the carbonyl compound represented by general formula (Ic)above is preferably a carbonyl compound represented by general formula(Id) below:

In general formula (IId), G⁴ and G⁵ each independently represent ahydrogen atom, an alkyl group having from 1 to 4 carbons, an alkenylgroup having from 1 to 4 carbons, a substituted or unsubstituted phenylgroup, naphthyl group, or benzyl group, and G⁴ and G⁵ may be bonded toeach other and, together with a carbon atom to which G⁴ and G⁵ arebonded, form a ring. R, X, and m are the same as R, X, and m in generalformula (IIa) above, respectively.

In general formula (Id), X, G⁴, G⁵, and m are the same as X, G⁴, G⁵, andm in general formula (IId) above, respectively.

Furthermore, in the method of producing a carbonyl compound according tothe present invention, G⁴ and G⁵ are preferably each independently ahydrogen atom or an alkyl group having from 1 to 4 carbons.

Furthermore, in the method of producing a carbonyl compound according tothe present invention, m is preferably an integer from 0 to 2; and whenm is 1 or 2, X is preferably a halogen atom.

Embodiments of the present invention will be described in further detailhereinafter using practical examples. Of course, the present inventionis not limited to the practical examples below, and it goes withoutsaying that various modes are possible with regard to the detailsthereof. Furthermore, the present invention is not limited to theembodiments described above, and various modifications are possiblewithin the scope indicated in the claims. Embodiments obtained byappropriately combining the technical means disclosed by the embodimentsare also included in the technical scope of the present invention. Inaddition, all of the documents cited in this specification are herebyincorporated by reference.

EXAMPLES Working Example 1 Synthesis of5-(4-chlorobenzyl)-2,2-bis((methoxymethoxy)methyl) cyclopentanone

Dimethylacetamide (1 mL), triethylamine (1.5 mL, 0.0482×2.2 mol), andacetic acid (0.58 mL, 0.0482×2.1 mol) were added to1-(4-chlorobenzyl)-3,3-bis((methoxymethoxy)methyl)-2-oxocyclopentanecarboxylic acid methyl ester (2.0 g, 0.00482 mol), an isobaric droppingfunnel was mounted between a cooling condenser and the reaction vessel,and they were stirred at 155° C. for 5 hours such that the distillationproduct did not return, and then they were reacted at 165° C. for 18hours. In the reaction liquid, ethyl acetate and saturated sodiumbicarbonate water were added, and the mixture was partitioned. Afterextracting the aqueous layer using ethyl acetate, the organic layer wasdried using anhydrous sodium sulfate and concentrated. Thereafter, thedried and concentrated product was purified using a silica gel column,and a target product was obtained.

The yield in grams was 1.53 g, and the percent yield was 89%.

Working Example 2 Synthesis of2-(4-chlorobenzyl)-8,8-dimethyl-7,9-dioxaspiro[4.5]decan-1-one

Dimethylacetamide (1 mL) and triethylamine (1.7 mL, 0.00545×2.25 mol)were added to2-(4-chlorobenzyl)-8,8-dimethyl-1-oxo-7,9-dioxaspiro[4.5]decane-2-carboxylicacid methyl ester (2.0 g, 0.00546 mol), and acetic acid (0.63 mL,0.00545×2.0 mol) was also added, after which an isobaric dropping funnelwas mounted between a cooling condenser and the reaction vessel, andthey were stirred at 155° C. for 11 hours such that the distillationproduct did not return. Toluene was added to the reaction solution, andafter washing with saturated sodium bicarbonate water and saturatedbrine solution, the aqueous layer was extracted with toluene. Theorganic layer was dried with anhydrous sodium sulfate and concentrated,and then the resulting substance was purified by silica gel columnchromatography to obtain the target product.

The yield in grams was 1.59 g, and the percent yield was 94%.

Working Example 3 Synthesis of 5-(4-chlorobenzyl)-2,2-dimethylcyclopentanone

Dimethylacetamide (1.5 mL), sodium acetate (0.042 g, 0.00509×0.1 mol),and triethylamine (1.2 mL, 0.00509×1.7 mol) were added to2-(4-chlorobenzyl)-1-oxo-7,9-dioxaspiro[4.5]decane-2-carboxylic acidmethyl ester (1.5 g, 0.00509 mol), and then acetic acid (0.44 mL,0.00509×1.5 mol) was added. An isobaric dropping funnel was mountedbetween a cooling condenser and the reaction vessel, and they werestirred at 165° C. for 24 hours such that the distillation product didnot return. Toluene and saturated sodium bicarbonate water were added tothe reaction solution, and after the mixture was partitioned, theaqueous layer was extracted with toluene. The organic layer was driedwith anhydrous sodium sulfate and concentrated, and then the resultingsubstance was purified by silica gel column chromatography to obtain thetarget product.

The yield in grams was 1.06 g, and the percent yield was 88%.

Working Example 4 Synthesis of 2-(4-chlorobenzyl) cyclopentanone

N,N-dimethylacetamide (1 mL) and pyridine (0.76 mL, 0.00375×2.5 mol)were added to 3-(4-chlorobenzyl)-2-oxocyclopentane carboxylic acidmethyl ester (1.0 g, 0.00375 mol), and then acetic acid (0.54 mL,0.00375×2.5 mol) was added. An isobaric dropping funnel was mountedbetween a cooling condenser and the reaction vessel, and they werestirred at 155° C. for 7 hours such that the distillation product didnot return. Ethyl acetate and saturated sodium bicarbonate water wereadded to the reaction solution, and after the mixture was partitioned,the aqueous layer was extracted with ethyl acetate. The organic layerwas dried with anhydrous sodium sulfate and concentrated, and then theresulting substance was purified by silica gel column chromatography toobtain the target product.

The yield in grams was 0.75 g, and the percent yield was 96%.

Working Example 5 Synthesis of 1-(4-chlorophenyl)ethanone

N,N-dimethylacetamide (1 mL) and pyridine (1.6 mL, 0.0047×2.5 mol) wereadded to 3-(4-chlorophenyl)-3-oxopropionic acid methyl ester (1.0 g,0.0047 mol), and then acetic acid (0.67 mL, 0.0047×2.5 mol) was added.In an argon atmosphere, an isobaric dropping funnel was mounted betweena cooling condenser and the reaction vessel, and they were reacted at155° C. for 9 hours such that the distillation product did not return.Ethyl acetate and saturated sodium bicarbonate water were added to thereaction solution, and after the mixture was partitioned, the aqueouslayer was extracted with ethyl acetate. The organic layer was dried withanhydrous sodium sulfate and concentrated, and then the resultingsubstance was purified by silica gel column chromatography to obtain thetarget product.

The yield in grams was 0.64 g, and the percent yield was 88%.

Comparative Example 1 Synthesis of5-(4-chlorobenzyl)-2,2-bis((methoxymethoxy)methyl) cyclopentanone

In isopropanol (5.5 mL),1-(4-chlorobenzyl)-3,3-bis((methoxymethoxy)methyl)-2-oxocyclopentanecarboxylic acid methyl ester (2.2895 g, 5.52 mmol) was dissolved, and a2 M sodium hydroxide solution (5.5 mL) was added thereto. The mixturewas stirred at 90° C. for 2 hours. Following the completion of thereaction, water was added, and the mixture was subjected to extractionusing ethyl acetate. The organic layer was washed with saturated brinesolution and water, and dried using anhydrous sodium sulfate. Thesolvent was distilled out, and the residue was purified using silica gelto obtain a target product.

The yield in grams was 1.3029 g, and the percent yield was 66%.

Reference Example 1 Synthesis 1 of2-(4-chlorobenzyl)-8,8-dimethyl-7,9-dioxaspiro[4.5]decan-1-one

Toluene (1 mL) was added to2-(4-chlorobenzyl)-8,8-dimethyl-1-oxo-7,9-dioxaspiro[4.5]decane-2-carboxylicacid methyl ester (10.0 g, 0.0273 mol), and then the resulting mixturewas suspended in 0.5 M sodium hydroxide aqueous solution (27.3 mL,0.0273 mol×0.5 mol), and reacted at 110° C. The reaction was continuedby adding a 0.5 M sodium hydroxide solution (27.3 mL, 0.0273 mol×0.5mol) every 2 hours (for three times total), and heating and stirringwere performed for total of 9 hours. Following the completion of thereaction, the mixture was allowed to cool to room temperature and thensubjected to extraction using toluene. The organic layer was washed withsaturated brine solution, and then dried using anhydrous sodium sulfate.Thereafter, the dried and concentrated product was purified using asilica gel column, and a target product was obtained.

The yield in grams was 6.75 g, and the percent yield was 80%.

INDUSTRIAL APPLICABILITY

The present invention can be used in the production of a2-benzyl-5,5-di(protected hydroxymethyl)-cyclopentanone derivativeserving as a raw material for an agricultural chemical or the like.

1. A method of producing a carbonyl compound represented by generalformula (I) below from a compound represented by general formula (II)below; the method comprising a step of subjecting the compoundrepresented by general formula (II) below to dealkoxycarbonylation inthe presence of an organic carboxylic acid salt of a tertiary amine:

in general formula (II), Z¹ represents a substituted or unsubstitutedalkyl group, cycloalkyl group, aryl group, or heterocyclic group; Z³ andZ² each independently represent a hydrogen atom, a substituted orunsubstituted alkyl group, cycloalkyl group, aryl group, or heterocyclicgroup; and R represents an alkyl group having from 1 to 4 carbons; Z¹and Z² may be bonded to each other;

in general formula (I), Z¹, Z², and Z³ are the same as Z¹, Z², and Z³ ingeneral formula (II) above, respectively.
 2. The method of producing acarbonyl compound according to claim 1, wherein a tertiary amineconstituting the organic carboxylic acid salt of a tertiary amine istriethylamine, trimethylamine, pyridine, or picoline.
 3. The method ofproducing a carbonyl compound according to claim 1, wherein an organiccarboxylic acid constituting the organic carboxylic acid salt of atertiary amine is an aliphatic monocarboxylic acid.
 4. The method ofproducing a carbonyl compound according to claim 1, wherein the organiccarboxylic acid salt of a tertiary amine is acetate of triethylamine orpyridine.
 5. The method of producing a carbonyl compound according toclaim 1, wherein an alkali metal salt of an organic carboxylic acid isfurther added in the reaction system.
 6. The method of producing acarbonyl compound according to claim 1, wherein the compound representedby general formula (II) above is a compound represented by generalformula (IIa) below; and the carbonyl compound represented by generalformula (I) above is a carbonyl compound represented by general formula(Ia) below:

in general formula (IIa), R represents an alkyl group having from 1 to 4carbons, Y represents an alkyl group or haloalkyl group having from 1 to6 carbons, an alkenyl group or haloalkenyl group having from 2 to 6carbons, an alkynyl group or haloalkynyl group having from 2 to 6carbons, or a group in which a part of hydrogen atoms of the alkylgroup, haloalkyl group, alkenyl group, haloalkenyl group, alkynyl group,or haloalkynyl group is substituted with —OG (G represents a protectinggroup of a hydroxy group); and n is an integer from 0 to 6; when n is 2or greater, a plurality of Y may be the same or different; when n is 2or greater, a plurality of Y may be bonded to each other and, togetherwith carbon atom(s) to which the plurality of Y are bonded, form a ring;X represents a halogen atom, an alkyl group having from 1 to 4 carbons,a haloalkyl group having from 1 to 4 carbons, an alkoxy group havingfrom 1 to 4 carbons, a haloalkoxy group having from 1 to 4 carbons, aphenyl group, a cyano group, or a nitro group; and m is an integer from0 to 5, when m is 2 or greater, a plurality of X may be the same ordifferent;

in general formula (Ia), X, Y, m, and n are the same as X, Y, m, and nin general formula (IIa) above, respectively.
 7. The method of producinga carbonyl compound according to claim 6, wherein the compoundrepresented by general formula (IIa) above is a compound represented bygeneral formula (IIb) below; and the carbonyl compound represented bygeneral formula (Ia) above is a carbonyl compound represented by generalformula (Ib) below:

in general formula (IIb), Y¹ and Y² each independently represent analkyl group or haloalkyl group having from 1 to 6 carbons, or a group inwhich a part of hydrogen atoms of the alkyl group or haloalkyl group issubstituted with —OG¹ (G¹ represents a protecting group of a hydroxygroup), and Y¹ and Y² may be bonded to each other and, together with acarbon atom to which Y¹ and Y² are bonded, form a ring; R, X, and m arethe same as R, X, and m in general formula (IIa) above, respectively;

in general formula (Ib), X, Y¹, Y², and m are the same as X, Y¹, Y², andm in general formula (IIb) above, respectively.
 8. The method ofproducing a carbonyl compound according to claim 7, wherein the compoundrepresented by general formula (IIb) above is a compound represented bygeneral formula (IIc) below; and the carbonyl compound represented bygeneral formula (Ib) above is a carbonyl compound represented by generalformula (Ic) below:

in general formula (IIc), G² and G³ each independently represent aprotecting group that dissociates under acidic conditions, and G² and G³may be bonded to each other; R, X, and m are the same as R, X, and m ingeneral formula (IIa) above, respectively;

in general formula (Ic), X, G², G³, and m are the same as X, G², G³, andm in general formula (IIc) above, respectively.
 9. The method ofproducing a carbonyl compound according to claim 8, wherein the organiccarboxylic acid salt of a tertiary amine is produced in a reactionsystem by adding a tertiary amine to a compound represented by generalformula (IIc) above and then adding an organic carboxylic acid in anamount smaller than the added amount of the tertiary amine, anddealkoxycarbonylation is performed.
 10. The method of producing acarbonyl compound according to claim 8, wherein the compound representedby general formula (IIc) above is a compound represented by generalformula (IId) below; and the carbonyl compound represented by generalformula (Ic) above is a carbonyl compound represented by general formula(Id) below:

in general formula (IId), G³ and G⁵ each independently represent ahydrogen atom, an alkyl group having from 1 to 4 carbons, an alkenylgroup having from 1 to 4 carbons, a substituted or unsubstituted phenylgroup, naphthyl group, or benzyl group, and G⁴ and G⁵ may be bonded toeach other and, together with a carbon atom to which G⁴ and G⁵ arebonded, form a ring; R, X, and m are the same as R, X, and m in generalformula (IIa) above, respectively;

in general formula (Id), X, G⁴, G⁵, and m are the same as X, G⁴, G⁵, andm in general formula (IId) above, respectively.
 11. The method ofproducing a carbonyl compound according to claim 10, wherein G⁴ and G⁵are each independently a hydrogen atom or an alkyl group having from 1to 4 carbons.
 12. The method of producing a carbonyl compound accordingto claim 6, wherein m is an integer from 0 to 2; and when m is 1 or 2, Xis a halogen atom.